DESCRIPTION: (Applicant's Abstract) The research goals are to use P50 and P3A event-related potentials (ERPs) to (1) study chronic cocaine abuse effects on CNS information processing, (2) to compare these effects with the effects of chronic alcohol abuse and cocaine-- alcohol co-abuse, (3) to determine the permanence of these effects during abstinence, (4) to determine whether these effects differ by gender and (S) to determine how these effects are effected both chronically and acutely by cigarette smoking. Amplitude and gating of the auditory middle-latency P50 response to repeated stimuli will be studied to assess neural systems affected by cholinergic, dopaminergic and non-adrenergic disturbances. Preliminary results show very large P50 amplitude and gating reductions in two week abstinent cocaine dependent individuals, but not in alcohol abusers. If these P50 disturbances reflect damage to neuronal system or pathways, they should be relatively permanent. If they reflect neurotransmitter system disturbance, they may resolve during persistent abstinence and may be used to evaluate pharmacological treatments designed to impact these specific neurotransmitters systems in cocaine addiction. Cigarette smoking temporarily normalizes P50 gating in schizophrenics, and it has been suggested that nicotine may transiently treat part of the information processing abnormality in schizophrenia We will test the hypothesis that cigarette smoking in cocaine abusers also transiently normalizes cocaine-abuse associated P50 abnormalities. Increased latency of the P3A ERP component is potential objective and sensitive early measure of information processing abnormalities secondary to chronic cocaine abuse and does not suffer from many of the problems inherent in neuropsychological testing. Preliminary results demonstrate increased P3A latency is a sensitive indicator of CNS disturbance in a variety of diseases (e.g., HIV disease, Alzheimer's disease) and as a result of drug use. We will study recently abstinent male and female samples of cocaine dependent, alcohol dependent, cocaine/alcohol co-dependent and control subjects who were never substance dependent. We will study these samples supplemented by samples to control for nicotine co-dependence. We will study all cocaine and/or alcohol dependent subjects at two weeks abstinence, six weeks abstinence and six mon abstinence. All subjects who are cigarette smokers will be tested on two days at each testing period, on one day they will be studied twelve hours after their last cigarette; on the other day immediately after a cigarette. Finally, samples of active cocaine abusers will be studied.